tbuckley/cabot-search huggingface dataset:
TMIC-38. MITOCHONDRIAL ATP BIOGENESIS REGULATED BY VDAC1 IN TMEM119+ TUMOR-ASSOCIATED MICROGLIA AND MACROPHAGES MEDIATES HIGH-GRADE GLIOMA GROWTH
Authors: Caren Wu, Yiyun Chen, Ya-Jui Lin, Kuo-Chen Wei, Kwang-Yu Chang, Li-Ying Feng, An-Chih Wu, Ko-Ting Chen, Alexander Liang Ren, Ryan Nitta, Janet Wu, Ayush Pant, Kwang Bog Cho, Crystal Mackall, Jian-Ying Chuang, Chiung-Yin Huang, Gordon Li, Christopher Jackson, Pin-Yuan Chen, Michael Lim
Journal: Neuro-Oncology (2023)

Abstract Patients with high-grade glioma have a poor prognosis and an average survival of less than 15 months, which is associated with an increase in tumor-associated microglia and macrophages (TAMs). TAMs in the glioma microenvironment are traditionally thought to suppress antitumor immune responses and are metabolically reprogrammed by glioma. However, it is unknown whether metabolic processes, like ATP synthesis, in TAMs can directly affect glioma growth. Through RNAseq, we identified a novel subpopulation that had elevated metabolic expression patterns. These TAMs (TMEM119+) had increased protein expression of ATP synthases and VDAC1, and surprisingly only TAMs located within the tumor center had increased mitochondrial energy potential. In vitro and ex vivo co-culture assays determined that activated TAMs increased the expression of metabolic, growth, and survival genes in high-grade glioma cells. These activated TAMs produced higher levels of extracellular ATP, which in turn increased glioma cell viability. Inhibition studies identified P2X purinoceptor 7 (P2X7R) as a key player in the TAMs ATP-induced glioma survival. Our findings demonstrate for the first time that a subpopulation of TAMs induced a more tumorigenic microenvironment through the secretion of ATP.
Chemokine CCL19 promotes type 2 T-cell differentiation and allergic airway inflammation
Authors: Keiko Nakano, Gregory S. Whitehead, Miranda R. Lyons-Cohen, Sara A. Grimm, Christina L. Wilkinson, Gentaro Izumi, Alessandra Livraghi-Butrico, Donald N. Cook, Hideki Nakano
Journal: Journal of Allergy and Clinical Immunology (2023)
Thrombopoietin mimetic‐induced bone marrow fibrosis
Authors: Kirsteen Harper, Catherine Bagot, Mike Leach, Barbara J. Bain
Journal: American Journal of Hematology (2023)

Thrombopoietin receptor agonists (TPO-RA) stimulate megakaryopoiesis and can increase platelet production in ITP. An increase in bone marrow reticulin is a well-recognized phenomenon1 though clinically significant, severe grades with collagen deposition are rare. Discontinuation of TPO-RA may not be necessary in all cases but has been shown to lead to regression of bone marrow fibrosis in cases reported. The authors declare no conflicts of interest.
The Future of Clinical Trials
Authors: Adrian F. Hernandez, Christopher J. Lindsell
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
<scp>VEXAS</scp> syndrome: Clinical, hematologic features and a practical approach to diagnosis and management
Authors: Matthew J. Koster, Terra L. Lasho, Horatiu Olteanu, Kaaren K. Reichard, Abhishek Mangaonkar, Kenneth J. Warrington, Mrinal M. Patnaik
Journal: American Journal of Hematology (2023)

Abstract VEXAS (Vacuoles, E1 enzyme, X‐linked, Autoinflammatory, Somatic) syndrome is a newly identified disease caused by somatic alterations in UBA1 which produce a recalcitrant inflammatory state along with hematologic disturbances. Patients with VEXAS can have a wide spectrum of clinical symptoms and providers should be familiar with the heterogeneity of associated clinical features. While hematologic parameters may be generally non‐specific, peripheral blood features of macrocytosis, monocytopenia, and/or thrombocytopenia coupled with bone marrow vacuolization of erythroid or myeloid precursors should raise suspicion for this condition. Due to an increased mortality, prompt recognition and accurate diagnosis is paramount. Access to testing for confirmation of UBA1 variants is not yet universally available but clinicians should understand the current available options for genetic confirmation of this disease. Treatment options are limited due to lack of prospective clinical trials but cytokine directed therapies such as interleukin‐6 inhibitors and JAK–STAT inhibitors as well as hypomethylating agents such as azacitidine have shown evidence of partial effect. Though cases are limited, allogeneic stem cell transplantation holds promise for durable response and potential cure. The intent of this review is to outline the pathophysiology of VEXAS syndrome and to provide a practical approach to diagnosis and treatment.
Restrictive or Liberal Transfusion Strategy in Myocardial Infarction and Anemia
Authors: Jeffrey L. Carson, Maria Mori Brooks, Paul C. Hébert, Shaun G. Goodman, Marnie Bertolet, Simone A. Glynn, Bernard R. Chaitman, Tabassome Simon, Renato D. Lopes, Andrew M. Goldsweig, Andrew P. DeFilippis, J. Dawn Abbott, Brian J. Potter, Francois Martin Carrier, Sunil V. Rao, Howard A. Cooper, Shahab Ghafghazi, Dean A. Fergusson, William J. Kostis, Helaine Noveck, Sarang Kim, Meechai Tessalee, Gregory Ducrocq, Pedro Gabriel Melo de Barros e Silva, Darrell J. Triulzi, Caroline Alsweiler, Mark A. Menegus, John D. Neary, Lynn Uhl, Jordan B. Strom, Christopher B. Fordyce, Emile Ferrari, Johanne Silvain, Frances O. Wood, Benoit Daneault, Tamar S. Polonsky, Manohara Senaratne, Etienne Puymirat, Claire Bouleti, Benoit Lattuca, Harvey D. White, Sheryl F. Kelsey, P. Gabriel Steg, John H. Alexander
Journal: New England Journal of Medicine (2023)

A strategy of administering a transfusion only when the hemoglobin level falls below 7 or 8 g per deciliter has been widely adopted. However, patients with acute myocardial infarction may benefit from a higher hemoglobin level.
Incorporating radiation with anti‐CD19 chimeric antigen receptor T‐cell therapy for relapsed/refractory non‐Hodgkin lymphoma: A multicenter consensus approach
Authors: Omran Saifi, Scott C. Lester, William G. Breen, William G. Rule, Yi Lin, N. Nora Bennani, Allison Rosenthal, Javier Munoz, Hemant S. Murthy, Mohamed A. Kharfan‐Dabaja, Jennifer L. Peterson, Bradford S. Hoppe
Journal: American Journal of Hematology (2023)

Abstract Anti‐CD19 chimeric antigen receptor T‐cell therapy (CART) has revolutionized the outcomes of relapsed and/or refractory B‐cell non‐Hodgkin lymphoma. However, CART is still limited by its availability, toxicity, and response durability. Not all patients make it to the CART infusion phase due to disease progression. Among those who receive CART, a significant number of patients experience life‐threatening cytokine release syndrome toxicity, and less than half maintain a durable response with the majority relapsing in pre‐existing sites of disease present pre‐CART. Radiation therapy stands as a promising peri‐CART and salvage treatment that can improve the outcomes of these patients. Evidence suggests that bridging radiotherapy prior to CART controls the disease during the manufacturing period, augments response rates and local control, cytoreduces/debulks the disease and decreases the severity of cytokine release syndrome, and may prolong disease‐free intervals and survival especially in patients with bulky disease. Consolidative radiotherapy for residual post‐CART disease alters the pattern of relapse and improves local recurrence‐free and progression‐free survivals. Salvage radiotherapy for relapsed post‐CART disease has favorable survival outcomes when delivered comprehensively for patients with limited relapsed disease and palliates symptoms for patients with diffuse relapsed disease. The biology of the disease during the peri‐CART period is poorly understood, and further studies investigating the optimal timing and dosing of radiation therapy (RT) are needed. In this review, we tackle the most significant challenges of CART, review and propose how RT can help mitigate these challenges, and provide The Mayo Clinic experts' approach on incorporating RT with CART.
Phase II clinical trial of neoadjuvant anti-PD-1 (toripalimab) combined with axitinib in resectable mucosal melanoma
Authors: B. Lian, Z. Li, N. Wu, M. Li, X. Chen, H. Zheng, M. Gao, D. Wang, X. Sheng, H. Tian, L. Si, Z. Chi, X. Wang, Y. Lai, T. Sun, Q. Zhang, Y. Kong, G.V. Long, J. Guo, C. Cui
Journal: Annals of Oncology (2023)

BackgroundThe outcome of patients with resectable mucosal melanoma is poor. Toripalimab combined with axitinib has shown impressive results in metastatic mucosal melanoma with an objective response rate of 48.3% and a median progression free survival of 7.5 months in a phase 1b trial. It was hypothesized that this combination administered in the neoadjuvant setting might induce a pathologic response in resectable mucosal melanoma, so we conducted this trial.Patients and methodsThis single-arm phase II trial enrolled patients with resectable mucosal melanoma. Patients received toripalimab 3 mg/kg Q2W plus axitinib 5 mg BID for 8 weeks as neoadjuvant therapy, then surgery and adjuvant toripalimab 3 mg/kg Q2W starting 2±1week after surgery for 44 weeks. The primary end point is the pathologic response rate according to International Neoadjuvant Melanoma Consortium recommendations.ResultsBetween Aug 2019 and Oct 2021, 29 patients were enrolled and received treatment, of whom 24 underwent resection. Median follow-up time was 34.2 months (95% CI [20.4 to 48.0]). The pathologic response rate was 33.3% (8/24, 4 pCR, 4pPR). Median event free survival for all patients was 11.1 months (95% CI [5.3, 16.9]). Median OS was not reached. Neoadjuvant therapy was tolerable with 8 (27.5%) grade 3-4 treatment related AEs and no treatment-related deaths. Tissue samples of 17 patients at baseline and after surgery were collected (5 responders and 12 non-responders). Multiplex IHC demonstrated a significant increase of CD3+ (p=0.0032) and CD3+CD8+ (p=0.0038) tumor-infiltrating lymphocytes after neoadjuvant therapy, particularly in pathological responders.ConclusionNeoadjuvant toripalimab combined with axitinib in resectable mucosal melanoma demonstrated a promising pathologic response rate with significantly increased infiltrating CD3+ and CD3+CD8+ T cells after therapy.Clinical trial informationNCT04180995.
Innovation in Event Adjudication—Human vs Machine
Authors: Kenneth W. Mahaffey, C. Michael Gibson, Renato D. Lopes
Journal: JAMA Cardiology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Natural Language Processing for Adjudication of Heart Failure in a Multicenter Clinical Trial
Authors: Jonathan W. Cunningham, Pulkit Singh, Christopher Reeder, Brian Claggett, Pablo M. Marti-Castellote, Emily S. Lau, Shaan Khurshid, Puneet Batra, Steven A. Lubitz, Mahnaz Maddah, Anthony Philippakis, Akshay S. Desai, Patrick T. Ellinor, Orly Vardeny, Scott D. Solomon, Jennifer E. Ho
Journal: JAMA Cardiology (2023)

The gold standard for outcome adjudication in clinical trials is medical record review by a physician clinical events committee (CEC), which requires substantial time and expertise. Automated adjudication of medical records by natural language processing (NLP) may offer a more resource-efficient alternative but this approach has not been validated in a multicenter setting.
A Placebo-Controlled Trial of Percutaneous Coronary Intervention for Stable Angina
Authors: Christopher A. Rajkumar, Michael J. Foley, Fiyyaz Ahmed-Jushuf, Alexandra N. Nowbar, Florentina A. Simader, John R. Davies, Peter D. O’Kane, Peter Haworth, Helen Routledge, Tushar Kotecha, Reto Gamma, Gerald Clesham, Rupert Williams, Jehangir Din, Sukhjinder S. Nijjer, Nick Curzen, Neil Ruparelia, Manas Sinha, Jason N. Dungu, Sashiananthan Ganesananthan, Ramzi Khamis, Lal Mughal, Tim Kinnaird, Ricardo Petraco, James C. Spratt, Sayan Sen, Joban Sehmi, David J. Collier, Afzal Sohaib, Thomas R. Keeble, Graham D. Cole, James P. Howard, Darrel P. Francis, Matthew J. Shun-Shin, Rasha K. Al-Lamee
Journal: New England Journal of Medicine (2023)

Percutaneous coronary intervention (PCI) is frequently performed to reduce the symptoms of stable angina. Whether PCI relieves angina more than a placebo procedure in patients who are not receiving antianginal medication remains unknown. We conducted a double-blind, randomized, placebo-controlled trial of PCI in patients with stable angina. Patients stopped all antianginal medications and underwent a 2-week symptom assessment phase before randomization. Patients were then randomly assigned in a 1:1 ratio to undergo PCI or a placebo procedure and were followed for 12 weeks. The primary end point was the angina symptom score, which was calculated daily on the basis of the number of angina episodes that occurred on a given day, the number of antianginal medications prescribed on that day, and clinical events, including the occurrence of unblinding owing to unacceptable angina or acute coronary syndrome or death. Scores range from 0 to 79, with higher scores indicating worse health status with respect to angina. A total of 301 patients underwent randomization: 151 to the PCI group and 150 to the placebo group. The mean (±SD) age was 64±9 years, and 79% were men. Ischemia was present in one cardiac territory in 242 patients (80%), in two territories in 52 patients (17%), and in three territories in 7 patients (2%). In the target vessels, the median fractional flow reserve was 0.63 (interquartile range, 0.49 to 0.75), and the median instantaneous wave-free ratio was 0.78 (interquartile range, 0.55 to 0.87). At the 12-week follow-up, the mean angina symptom score was 2.9 in the PCI group and 5.6 in the placebo group (odds ratio, 2.21; 95% confidence interval, 1.41 to 3.47; P<0.001). One patient in the placebo group had unacceptable angina leading to unblinding. Acute coronary syndromes occurred in 4 patients in the PCI group and in 6 patients in the placebo group. Among patients with stable angina who were receiving little or no antianginal medication and had objective evidence of ischemia, PCI resulted in a lower angina symptom score than a placebo procedure, indicating a better health status with respect to angina. (Funded by the National Institute for Health and Care Research Imperial Biomedical Research Centre and others; ORBITA-2 ClinicalTrials.gov number, NCT03742050.)
Cumulative exposure to metabolic syndrome affects the risk of psoriasis differently according to age group: a nationwide cohort study in S. Korea
Authors: Se Young Jung, Kyungdo Han, Jin Hyung Jung, Hyunsun Park, Dong Wook Shin
Journal: British Journal of Dermatology (2023)

Late-onset psoriasis is more associated with the cumulative metabolic syndrome burden in the oldest age group, suggesting the particular importance of managing metabolic syndrome in midlife and beyond.
Thinking small to win big? A critical review on the potential application of extracellular vesicles for biomarker discovery and new therapeutic approaches in pancreatic cancer
Authors: Mahrou Vahabi, Annalisa Comandatore, Chiara Centra, Giovanni Blandino, Luca Morelli, Elisa Giovannetti
Journal: Seminars in Cancer Biology (2023)

Pancreatic ductal adenocarcinoma (PDAC) is an extremely deadly form of cancer, with limited progress in 5-year survival rates despite significant research efforts. The main challenges in treating PDAC include difficulties in early detection, and resistance to current therapeutic approaches due to aggressive molecular and microenvironment features. These challenges emphasize the importance of identifying clinically validated biomarkers for early detection and clinical management. Extracellular vesicles (EVs), particularly exosomes, have emerged as crucial mediators of intercellular communication by transporting molecular cargo. Recent research has unveiled their role in initiation, metastasis, and chemoresistance of PDAC. Consequently, utilizing EVs in liquid biopsies holds promise for the identification of biomarkers for early detection, prognosis, and monitoring of drug efficacy. However, numerous limitations, including challenges in isolation and characterization of homogeneous EVs populations, as well as the absence of standardized protocols, can affect the reliability of studies involving EVs as biomarkers, underscoring the necessity for a prudent approach. EVs have also garnered considerable attention as a promising drug delivery system and novel therapy for tumors. The loading of biomolecules or chemical drugs into exosomes and their subsequent delivery to target cells can effectively impede tumor progression. Nevertheless, there are obstacles that must be overcome to ensure the accuracy and efficacy of therapies relying on EVs for the treatment of tumors. In this review, we examine both recent advancements and remaining obstacles, exploring the potential of utilizing EVs in biomarker discovery as well as for the development of drug delivery vehicles.
Relapse of acute myeloid leukemia after allogeneic stem cell transplantation: immune escape mechanisms and current implications for therapy
Authors: Tatjana Sauerer, Giuliano Filippini Velázquez, Christoph Schmid
Journal: Molecular Cancer (2023)

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by the expansion of immature myeloid cells in the bone marrow (BM) and peripheral blood (PB) resulting in failure of normal hematopoiesis and life-threating cytopenia. Allogeneic hematopoietic stem cell transplantation (allo-HCT) is an established therapy with curative potential. Nevertheless, post-transplant relapse is common and associated with poor prognosis, representing the major cause of death after allo-HCT. The occurrence of relapse after initially successful allo-HCT indicates that the donor immune system is first able to control the leukemia, which at a later stage develops evasion strategies to escape from immune surveillance. In this review we first provide a comprehensive overview of current knowledge regarding immune escape in AML after allo-HCT, including dysregulated HLA, alterations in immune checkpoints and changes leading to an immunosuppressive tumor microenvironment. In the second part, we draw the line from bench to bedside and elucidate to what extend immune escape mechanisms of relapsed AML are yet exploited in treatment strategies. Finally, we give an outlook how new emerging technologies could help to improve the therapy for these patients, and elucidate potential new treatment options.
Arrhythmic Risk in Biventricular Pacing Compared With Left Bundle Branch Area Pacing: Results From the I-CLAS Study
Authors: Bengt Herweg, Parikshit S. Sharma, Óscar Cano, Shunmuga Sundaram Ponnusamy, Francesco Zanon, Marek Jastrzebski, Jiangang Zou, Mihail G. Chelu, Kevin Vernooy, Zachary I. Whinnett, Girish M. Nair, Manuel Molina-Lerma, Karol Curila, Dipen Zalavadia, Cicely Dye, Sharath C. Vipparthy, Ryan Brunetti, Mishal Mumtaz, Pawel Moskal, Andrew M. Leong, Antonius van Stipdonk, Jerin George, Yusuf K. Qadeer, Jeffrey Kolominsky, Mehrdad Golian, Ramez Morcos, Lina Marcantoni, Faiz A. Subzposh, Kenneth A. Ellenbogen, Pugazhendhi Vijayaraman
Journal: Circulation (2023)

Left bundle branch area pacing (LBBAP) may be associated with greater improvement in left ventricular ejection fraction and reduction in death or heart failure hospitalization compared with biventricular pacing (BVP) in patients requiring cardiac resynchronization therapy. We sought to compare the occurrence of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) and new-onset atrial fibrillation (AF) in patients undergoing BVP and LBBAP.
Atomic force microscopy-mediated mechanobiological profiling of complex human tissues
Authors: David H. Cho, Sebastian Aguayo, Alexander X. Cartagena-Rivera
Journal: Biomaterials (2023)

Tissue mechanobiology is an emerging field with the overarching goal of understanding the interplay between biophysical and biochemical responses affecting development, physiology, and disease. Changes in mechanical properties including stiffness and viscosity have been shown to describe how cells and tissues respond to mechanical cues and modify critical biological functions. To quantitatively characterize the mechanical properties of tissues at physiologically relevant conditions, atomic force microscopy (AFM) has emerged as a highly versatile biomechanical technology. In this review, we describe the fundamental principles of AFM, typical AFM modalities used for tissue mechanics, and commonly used elastic and viscoelastic contact mechanics models to characterize complex human tissues. Furthermore, we discuss the application of AFM-based mechanobiology to characterize the mechanical responses within complex human tissues to track their developmental, physiological/functional, and diseased states, including oral, hearing, and cancer-related tissues. Finally, we discuss the current outlook and challenges to further advance the field of tissue mechanobiology. Altogether, AFM-based tissue mechanobiology provides a mechanistic understanding of biological processes governing the unique functions of tissues.
SELECTing Treatments for Cardiovascular Disease — Obesity in the Spotlight
Authors: Amit Khera, Tiffany M Powell-Wiley
Journal: New England Journal of Medicine (2023)

Overweight and obesity have reached epidemic proportions, affecting more than 70% of the U.S. adult population and more than 50% of persons worldwide.1 In addition to numerous health consequences, obesity contributes to cardiovascular disease indirectly through the development of risk factors and directly through various biologic mechanisms.2 There is a clear need to redouble efforts to target obesity-related cardiometabolic risk as a strategy for combating cardiovascular disease.3 However, until recently, few pharmacologic tools were available to safely and effectively lower body weight. Medications that include glucagon-like peptide-1 (GLP-1) receptor agonist components have now been shown to produce substantial weight loss . . .